Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance-Reference-Cited by-同舟云学术

Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance

Published:2023-12 Issue:12 Volume:7 Page:
ISSN:2471-254X
Container-title:Hepatology Communications
language:en
Short-container-title:

Author:

Teckman Jeffrey¹,Rosenthal Philip²,Ignacio Rosalinda V.³,Spino Cathie³,Bass Lee M.⁴,Horslen Simon⁵,Wang Kasper⁶,Magee John C.⁷,Karpen Saul⁸,Asai Akihiro⁹,Molleston Jean P.¹⁰,Squires Robert H.¹¹,Kamath Binita M.¹²,Guthery Stephen L.¹³,Loomes Kathleen M.¹⁴,Shneider Benjamin L.¹⁵,Sokol Ronald J.¹⁶,

Affiliation:

1. Department of Pediatrics and Biochemistry, Saint Louis University, Cardinal Glennon Children’s Hospital, Saint Louis, Missouri, USA

2. Department of Pediatrics and Surgery, University of California San Francisco, San Francisco, California, USA

3. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA

4. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

5. Department of Pediatric Gastroenterology and Hepatology, Seattle Children’s Hospital, University of Washington School of Medicine, Seattle, Washington, USA

6. Department of Pediatric Gastroenterology, Children’s Hospital Los Angeles, Los Angeles, California, USA

7. Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan, USA

8. Department of Pediatrics, Emory University, Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

9. Department of Gastroenterology, and Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

10. Department of Pediatric Gastroenterology, Hepatology and Nutrition, James Whitcomb Riley Hospital for Children, Indianapolis, Indiana, USA

11. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

12. Division of Pediatric Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

13. Department of Pediatrics, University of Utah College of Medicine and Intermountain Primary Children’s Hospital, Salt Lake City, Utah, USA

14. Division of Pediatric Gastroenterology, Department of Pediatrics, Hepatology and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

15. Department of Pediatric Gastroenterology, Hepatology and Nutrition, Baylor College of Medicine, Texas Children’s Hospital, Houston, Texas, USA

16. Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Children’s Hospital Colorado, Aurora, Colorado, USA

Abstract

Background: Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood. Methods: The Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred enrolled; first, those presenting with neonatal cholestasis captured by a unique study, enrolled because of neonatal cholestasis but before specific diagnosis, then followed longitudinally (n=46); second, separately, all participants who progressed to liver transplant (n=119). Results: We found male predominance for neonatal cholestasis in AATD (65% male, p=0.04), an association of neonatal gamma-glutamyl transpeptidase elevation to more severe disease, and a higher rate of neonatal cholestasis progression to portal hypertension than previously reported (41%) occurring at median age of 5 months. Participants with and without preceding neonatal cholestasis were at risk of progression to transplant. Participants who progressed to liver transplant following neonatal cholestasis were significantly younger at transplant than those without neonatal cholestasis (4.1 vs. 7.8 years, p=0.04, overall range 0.3–17 years). Neonatal cholestasis had a negative impact on growth parameters. Coagulopathy and varices were common before transplant, but gastrointestinal bleeding was not. Conclusions: Patients with AATD and neonatal cholestasis are at risk of early progression to severe liver disease, but the risk of severe disease extends throughout childhood. Careful attention to nutrition and growth is needed.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Hepatology

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